versão impressa ISSN 1415-790X
Rev. bras. epidemiol. vol.15 no.3 São Paulo Set. 2012
Priscila Bernardina M. SoaresI; Sidinei Quirino FilhoII; William Pereira de SouzaII; Renata Cristina R. GonçalvesIII; Daniella Reis B. MartelliIV; Marise Fagundes SilveiraIV; Hercílio Martelli JúniorIV
de Oncologia da Santa Casa de Misericórdia de Montes Claros, MG
IIIniciação Científica do Curso de Medicina da Universidade Estadual de Montes Claros - Unimontes, MG
IIIDepartamento de Oncologia da Santa Casa de Misericórdia de Montes Claros, MG
IVCentro de Ciências Biológicas e da Saúde da Universidade Estadual de Montes Claros - Unimontes, MG
To describe the main characteristics, including stage of disease and local treatment
of patients admitted to two reference services for the treatment of breast cancer
in the North of Minas Gerais.
METHODS: We conducted a cross-sectional descriptive study. We evaluated medical records of 288 female patients with breast cancer admitted between January 2006 and December 2009, referred from a public hospital and a private clinic. Variables were analyzed using the chi-square test and multinomial logistic regression.
RESULTS: 68.1% of patients were referred from the public hospital. There was a predominance of patients over 50 years old (54.5%), married (59%) and with children (87.8%). The mean age of the population studied was 63 years old. Time between suspected cancer and confirmation of diagnosis was over six months in 42.7% of patients. Cancer diagnosis was late (stage III and IV) in 47.6% of patients. Family history of breast cancer was present in 20.1%, 20.8% of them had performed self-breast examination, and 41% had been submitted to a mammogram.
CONCLUSION: There was a higher prevalence of stage III/IV patients from the public service when compared to the private sector. We found that the major factors associated with the late diagnosis of breast cancer were the delay between suspected and confirmed diagnosis, the absence of family history of breast cancer and not having a mammogram.
Keywords: Breast cancer. Epidemiology. Late diagnosis. Health services. Risk Factors.
Cancer is a relevant public health problem worldwide, accounting for 7 million deaths annually1. Tumors in the following organs are associated with the highest mortality rates: lungs, stomach, colon and breasts. It is estimated that by 2020 there will be 15 million new cancer cases annually, of which 60% will occur in developing countries1.
Breast cancer is a malignant neoplasm more frequently found in women, totaling 23% of all cancer cases worldwide2. Annually, more than one million women are diagnosed with this disease in the world and more than 410,000 will die from it3. This neoplasm is more frequent in developed countries and the highest incidences are found in the United Kingdom, Australia, the USA and Canada1. Although the mortality of patients with breast cancer has still shown an increasing trend in several countries for several years, developed countries such as the USA, United Kingdom and Australia have already recorded a reduction in mortality4, which is attributed to the increasing use of mammography and early disease treatment5. In general, the mean survival rate of patients with breast cancer is higher than five years in developed countries such as the USA, Canada, Japan and certain Western European countries and lower in developing countries such as Algeria, Brazil and Eastern European countries6,7. Such differences in survival rate can be explained by the greater development in diagnosis in developing countries8.
In Brazil, it was estimated that by 2010 there would be 49,240 new cases of breast cancer and an estimated risk of 49 cases per 100,000 women. In the Southeast region, breast cancer is more frequent among women, with an estimated risk of 65 new cases per 100,000 women9. In the state of Minas Gerais in particular, between 1998 and 2007, approximately 85,000 new cancer cases occurred, of which 14,363 were breast cancer, nearly 17% of the total10. In addition, it is the most important cause of death from cancer in the Brazilian female population and it is likely that diagnosing this disease in a more advanced stage is the main responsible for the continuing high mortality rates9.
Studies have suggested that factors such as lack of access to health services and delays in the investigation of suspicious breast lesions and in disease treatment implementation have contributed to late diagnosis and, consequently, to a high mortality from breast cancer11-17. Thus, the present study aimed to describe the main characteristics of patients with breast cancer admitted to two cancer referral services, one public and the other private.
A cross-sectional descriptive study was conducted. Researchers assessed a total of 288 medical records of patients admitted to two cancer referral services, one public and the other private, located in the city of Montes Claros, north of Minas Gerais, Brazil. The services mentioned used the same medical reports and therapeutic protocol. All patients with a histopathological diagnosis of breast carcinoma were included in this study, regardless of the clinical variables. Cases with a diagnosis of histological types of malignant breast neoplasm other than carcinomas and cases of breast cancer in males were excluded.
General and clinical information about patients were collected. General characteristics were as follows: age (categorized into three age groups), place of origin (Montes Claros and other cities), marital status (single, married, widowed, divorced/separated), professional activity (employed/self-employed, housewife/retired), religion (Catholic, Evangelical and others), number of children, smoking habit (yes or no), alcohol drinking (yes or no), and place of collection (public or private health service). With regard to clinical characteristics, the following variables were investigated: clinical stage of tumor (stage I, stage II, stages III/IV), length of time between clinical suspicion and diagnostic confirmation (zero to five months and more than five months), menopausal status (premenopausal and postmenopausal), presence of metastasis upon diagnosis (yes or no), mammogram performed (yes or no), breast self-exam performed (yes or no), surgical treatment (conservative surgery or mastectomy), family history of breast cancer (yes or no), chemotherapy performed (yes or no), radiotherapy performed (yes or no), hormone therapy performed (yes or no) and immunohistochemical profile of lesions (ER, PR, HER2 and triple-negative).
A descriptive analysis of general and clinical characteristics was performed using frequency distributions. Chi-square test was used to compare the frequency of clinical stage of the disease between the two health services.
In addition, bivariate and multiple analyses were performed and crude and adjusted prevalence ratios were estimated to assess the association between the "clinical stage" and the remaining characteristics of patients. To achieve this, stages III and IV were grouped, so that the outcome variable was categorized into three levels (stage I, stage II and stages III/IV). Consequently, the multinomial logistic model was adopted, whose reference category was Stage I. The significance level was set at p<0.05. The database was constructed using SPSSTM 17.0 (Statistical Package for Social Science for Windows, Inc., USA).
The present study was approved by the Research Ethics Committee of the Universidade Estadual de Montes Claros, Minas Gerais, Brazil, and both cancer referral services agreed to participate.
A total of 288 women with breast carcinomas, admitted to the public and private cancer referral services between 2006 and 2009, were included in this study. Table 1 shows the general characteristics of the population studied, whereas clinical characteristics are shown in Table 2. The majority of cases (68.1%) originated from the public health service; women aged more than 50 years (54.5%), married (59%), with children (87.8%) and postmenopausal (53.5%) predominated. The interval of time between the clinical suspicion and diagnostic confirmation was longer than six months in 42.7% of women; a late diagnosis (stages III and IV) was made in 47.6% and the percentages recorded in the public health service were higher than those found in the private service; 20.8% performed a breast self-exam; 41% had a mammogram; and 40.6% had a mastectomy. With regard to the immunohistochemical profile of lesions, 69.4% were positive ER, 26% had an overexpression of HER-2 and 18.4% were triple-negative.
In terms of disease stages, the public health service was compared to the private one and a higher frequency of patients in clinical stages III and IV was observed in the public service (53.6% versus 34.8%). On the other hand, when the initial diagnosis was analyzed (stage in situ/I), there was a higher frequency in the private service than in the public one (43.5% versus 14.8%), as shown in Graph 1. Table 3 shows an absence of association of age, menopausal status, occupation, immunohistochemical profile and breast self-exam with disease stages, using multinomial logistic regression and comparing stages II, III and IV with the initial stage (in situ/I). In a distinctive way, not having a mammogram (PRadjusted=5.10), the absence of a family history of breast cancer (PRadjusted=2.23 and 2.43) and the length of time between the clinical suspicion and diagnostic confirmation ≥ 6 months (PRadjusted=2.97 and 3.04) were associated with the more advanced clinical stages of disease.
Differently from several developed countries, Brazil has had an increase in the mortality rate from breast cancer in recent years, mainly because of late diagnosis and the delay in the implementation of adequate treatment, as this neoplasm is considered to be curable if diagnosed and treated early5-9. The present study enabled researchers to know the profile of women with breast cancer admitted to public and private referral centers located in the city of Montes Claros, north of Minas Gerais, to receive cancer treatment. The mean age of these women was 63 years. The youngest one was 27 years and the oldest one was 100 years, while the majority (54.5%) were aged 50 years and 53.5% were postmenopausal. Although age is a recognized risk factor for the development of breast cancer, this variable did not show an association between clinical stages of disease and diagnosis according to the results obtained. However, other studies suggest that breast cancer in younger women has a more aggressive physiopathology, contributing to late diagnosis, and the prognosis is worse when compared to breast tumors in older women18-23.
There was a predominance of married women (59%) and those with children (87.8%). In addition, marital status and the number of children did not interfere with the disease stages, although nulliparity is one of the risk factors associated with breast cancer24,25. Similarly, in a survival study conducted with 1,022 women with breast neoplasm, marital status was not considered to be an important factor26, which confirms the results from a systematic literature review performed by Ramirez et al13. Controversially, another study with 540 American female patients revealed that the fact of having never been married increased the risk of having the advanced stage of this disease by almost three times27.
Family history of breast cancer, reported by 20.1% of women in the present study, was associated with the stage of the disease upon diagnosis, confirming the findings of Hoskins et al28, which stated that up to 20% of women with breast cancer had a positive family history. According to cross-sectional studies conducted with a population of adult women in the United States, from 5% to 10% had a family history of stage I of breast cancer, suggesting that these women inherited a genetic mutation that puts them at an increased risk of developing breast and ovarian cancer28. A systematic review of 14 selected studies on risk factors for breast cancer in Brazilian women concluded that little is known about the prevalence of family history of breast cancer in the Brazilian population and found prevalence rates varying between 3.7% and 13.10%29. Another review of family history of breast cancer30 identified 74 published studies in which authors revealed an estimated relative risk (RR) associated with such family history of 2.0 (CI = 1.8-2.1) for a mother, 2.3 (CI = 2.1-2.4) for a sister and 3.6 (CI = 2.5-5) for a mother and sister. The risks increased when a first degree relative had been diagnosed before the age of 50 years31.
With regard to immunohistochemistry, the present study found a 26% of overexpression of HER-2 protein according to the medical records analyzed, whereas other studies32,33 confirmed the overproduction of this protein between 25 and 30% of breast tumors. This protein is associated with worse prognosis, high histological grade, and the reduction in time without disease and overall survival. The estrogen receptor (ER) is expressed in approximately 65% of cases diagnosed before menopause and in nearly 80% of those diagnosed after menopause, and it is usually associated with more favorable prognoses34. Likewise, 69.4% of all patients investigated in this study are ER positive. In addition, with regard to immunohistochemistry, Rakha et al35 identified triple-negative tumors, defined by the absence of expression of hormonal receptors and by the non-positivity of HER-2. It is believed that triple-negative breast cancer corresponds to approximately15% of cases, with a higher frequency in black women, those with BRCA1 mutations, and younger women36. Of all women analyzed in this study, 18.4% were triple-negative. However, although hormonal receptors and the expression of the HER-2 protein are related to the prognosis33,34, these variables were not associated with the stage level upon diagnosis in the present study.
A bivariate analysis of data was performed and found a higher percentage of women in stages III and IV, which was statistically more expressive in the public service than in the private one (53.6% versus 34.8%). In contrast, while 43.5% of women admitted to the private sector were considered to be in stage I, this group totaled 14.8% in the public sector, confirming the results of Rezende et al16, who identified 51% of women diagnosed between stages II and IV. Gonçalves et al37 emphasized that stage III was present in one third of Brazilian women admitted to breast cancer services. Likewise, another study38 analyzed 43,442 cases of breast cancer between 1995 and 2002 and revealed that 87.7% of women diagnosed with breast cancer were between stages II and IV (stage II=42.8%, stage III=32.6% and stage IV=12.3%). Whereas the standard mortality rates of breast cancer in developed countries decreased, Brazil had an increase in these rates during the same period (from 8.57 to 11.18/100,000 women). The median of percentage of patients between stages II and IV was 45.3% in Brazil and 12.1% in the United States38.
The monitoring method of breast self-examination, although not an appropriate technique for the early diagnosis of breast cancer, has been considered as an auxiliary method39. Several studies40-42 affirm that there has not been scientific evidence that such practice contributes to the reduction in mortality from this type of cancer. In the present study, not performing a breast self-exam was not associated with more advanced stages upon diagnosis. In contrast, having a mammogram as a more efficient method to monitor breast cancer had a positive impact on the mortality rate43, which could be reduced by 30% in the 40 to 69 year age group44. Types of cancer identified in asymptomatic women are likely to have smaller sizes and to be in the first stages45. Although there has been no consensus on guidance on breast cancer monitoring in the age groups of less than 50 years and more than 70 years46,47, since April 2009, the Brazilian Sistema Único de Saúde (SUS - Unified Health System) has guaranteed that mammograms for all women aged 40 years and more will be performed9. Similarly, this study pointed to mammography being more frequently performed in the private health service than in the public one and to not having a mammogram being associated with more advanced stages of breast cancer. Marchi et al48 conducted a cross-sectional study in which 643 women submitted to mammography were interviewed and observed that 472 of them were cared for in public health services and 171 in private health services. Among other characteristics, they assessed the use of mammography among users of public and private health services and concluded that the way they accessed these services influenced the proportion of women previously monitored by mammography, which was higher in the private health network48.
The present study showed a strong association of the interval of time between the clinical suspicion and diagnostic confirmation with the stage level upon diagnosis of cancer (PRadjusted=2.97 and 3.04). This interval was longer than six months in almost half of the women (42.7%), indicating the slowness of the city's health system in the period studied. These results confirm the conclusions of Rezende et al16, who conducted a study aimed at identifying the causes of delay in caring for women diagnosed with breast cancer in a tertiary hospital of the city of Rio de Janeiro, between January and July 2004, obtaining a median time of one month between the first sign or symptom of disease and the first consultation and of 6.5 months between this consultation and the diagnostic confirmation16. Similarly, while studying a cancer service of a public hospital of the city of São Paulo, Trufelli et al17 emphasized that the delay in the treatment of breast cancer cases was primarily associated with the length of time until the patient sought a health service to have a mammogram and biopsy of suspected lesions performed.
The epidemiological studies conducted showed that there are still important indicators of advanced breast cancer upon diagnosis in Brazil, a fact confirmed in the present study (47.6%). Not having a mammogram performed, the absence of a family history of breast cancer and the long interval of time between clinical suspicion and diagnostic confirmation were emphasized in this study as relevant factors associated with late diagnosis. Researchers observed the need to implement plans and actions aimed at reducing the delay in the treatment of breast cancer cases in public health services to increase the frequency of early detection and, consequently, the cure for this disease in Brazil.
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Correspondência: Received: 05/25/11
Priscila Bernardina Miranda Soares
Avenida Mestra Fininha, 1.951
CEP 39403-222 Montes Claros, MG
Final version: 11/24/11